Does Estrogen Replacement Prevent Dementia?
ABSTRACT & COMMENTARY
Synopsis: A comprehensive meta-analysis and literature review could not conclude whether estrogen replacement prevents dementia in healthy postmenopausal women.
Source: Yaffe K, et al. JAMA 1998;279:688-695.
More than 10% of all americans older than age 65 suffer from dementia. Yaffe and colleagues from the University of California, San Francisco, examined all existing peer-reviewed studies on the effects of estrogen on cognition and dementia. Seven randomized, controlled trials on estrogen's cognitive effects were too heterogeneous to be formally meta-analyzed, although six of the seven showed that healthy postmenopausal women on estrogen replacement therapy may improve various cognitive test scores, if only minimally.
In a separate meta-analysis of 10 observational studies, Yaffe et al found that when healthy postmenopausal women undergo estrogen replacement, they appear to have a 29% lower risk of developing dementia. As Yaffe et al readily state, however, the 10 observational studies were heterogeneous and all small.
Yaffe et al also reviewed the relevant biological literature. In animal and human studies, estrogen stimulates cholinergic and serotonergic activity in the central nervous system while blocking monoamine oxidase. Estrogen also appears to maintain neuronal function and prevent cerebral ischemia.
COMMENT BY ELIZABETH MORRISON, MD
As Yaffe et al said, "Summary findings from meta-analysis . . . are only as reliable as the findings of the individual studies." To date, studies on estrogen and cognition are too few, too small, and too inconclusive to permit the type of powerful meta-analysis that might help us counsel women about these critical issues while we await a large randomized trial.
Given that half of our postmenopausal patients are at eventual risk of developing dementia, clinicians are understandably eager for conclusive data. Yaffe et al cannot provide what we are looking for, but their work is still a useful step toward more concrete answers.
When we compare side-by-side the seven randomized, controlled trials on estrogen and cognitive test scores in healthy postmenopausal women, we see that, as a group, the trials are plagued by methodologic problems. Most trials included women who still complained of menopausal symptoms. Did estrogen directly improve their cognitive function, or did it simply improve their sleep and hot flushes, allowing them to concentrate on the cognitive tasks at hand? How would these women have fared in cognitive testing had they been taking progestins as well as estrogens? And, should we consider marginal cognitive improvements-on one or two of multiple test scores-as evidence of real benefit to these women?
I agree with Yaffe et al that we probably shouldn't. In describing their meta-analysis of 10 epidemiologic studies, Yaffe et al conclude that the apparent 29% decrease in dementia in healthy postmenopausal women taking estrogen may represent little more than a house of cards. Case-control and prospective cohort studies failed to produce data that were any more conclusive.
Cognitive benefits are probably not the major reason that physicians and patients are interested in hormone replacement therapy. Still, many of us will follow with avid interest the progress of large randomized, controlled trials looking at estrogens, progestins, and multiple outcomes (heart, bone, and cognition protection) in healthy postmenopausal women. Fortunately, one such multicenter trial, the well-known Women's Health Initiative, includes a large companion trial (the Women's Health Initiative Memory Study) that should provide definitive answers. Until then, regarding estrogen and cognition, our patients' guesses may be as good as ours.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content